Molecular mechanisms of transforming growth factor-beta signaling

The present experiments examined the effects of posttraining intrahippocampal injections of the degradative enzyme-resistant methylcarbamyl analog of the bioactive phospholipid platelet-activating factor (mc-PAF) and the platelet-activating factor (PAF) receptor antagonists BN52021 and BN 50730 on memory in male Long-Evans rats trained in a hidden platform version of the Morris water maze. Following an eight-trial training session, rats received a unilateral intrahippocampal injection of mc-PAF (0.5, 1.0, or 2.0 microgram/0.5 microliter), lyso-PAF (1.0 microgram/0.5 microliter), the cell surface PAF receptor antagonist BN 52021 (0.25, 0.5, or 1.0 micrigram/0.5 microliter/, the intracellular PAF receptor antagonist BN 50730 (2.0, 5.0, or 10.0 microgram/0.5 microliter), or vehicle (50% DMSO in 0.9% saline; 0.5 microliter). On a retention test conducted 24 h after training, the escape latencies of rats administered mc-PAF (1.0 or 2.0 microgram) were significantly lower than those of the vehicle-injected controls, demonstrating a memory-enhancing effect of mc-PAF. Injections of lyso-PAF, a structurally similar metabolite of PAF, had no influence on memory, indicating that the memory-enhancing effect of mc-PAF is not caused by membrane perturbation by the phospholipid. The retention test escape latencies of rats administered BN 52021 (0.5 microgram) and BN 50730 (5.0 or 10 microgram) were significantly higher than those of the controls, indicating a memory impairing effect of both PAF antagonists. When mc-PAF, BN 52021, or BN 50730 was administered 2 h posttraining, no effect on retention was observed, indicating a time-dependent effect of the neuroactive substances on memory storage. The findings suggest a role for endogenous PAF in hippocampal-dependent memory processes.     

Childhood personality influences on social-cognitive development: a longitudinal study

The relation of childhood personality to the development of friendship understanding and moral judgment in adolescence was considered in a longitudinal study. Personality at age 7, assessed with the California Child Q-Set, was characterized in terms of ego-resiliency and ego-control. IQ and social class were also measured. Friendship understanding was assessed when the participants were ages 7, 9, 12, 15, and 19, and moral judgment was elicited when the participants were 12, 15, and 19. Ego-resiliency was found to predict social-cognitive development in adolescence, even after the effects of IQ and childhood measures of social-cognitive development were controlled for. Analyses indicate that the effects of ego-resiliency on social-cognitive development are largely unmediated by the ability to focus attention or by social participation.     

Fibronectin fragments modulate human retinal capillary cell proliferation and migration

Capillary morphogenesis involves cell-cell and cell-matrix interactions. Proteases elaborated by capillary cells modify the extracellular matrix (ECM) to facilitate capillary tube formation. Previously, we detected the presence of fibronectin fragments (Fn-f) associated with the proform of matrix metalloprotease-2 (MMP-2) in conditioned medium of human retinal endothelial cells (HRECs). Association of this fragment to latent MMP-2 prevented autocatalytic activation of MMP-2, suggesting a modulatory role of Fn-f in MMP-2 activation. In this report, we examined the potential role of Fn-f on two processes involved in angiogenesis, proliferation and migration of vascular cells. The effects of Fn-f on proliferation were determined by DNA synthesis and cell counts. Their effects on migration were assessed using modified Boyden chambers. Seven Fn-f were tested on vascular cell migration and/or proliferation. Three Fn-f induced migration. Fn-f of 30-kDa and 120-kDa size positively affected proliferation of microvascular cells but not macrovascular cells. A 45-kDa gelatin binding fragment of Fn inhibited HREC proliferation but stimulated pericyte and smooth muscle cell proliferation. The potency of these fragments exceeded that of the known angiogenic growth factor, basic fibroblast growth factor (bFGF), on HREC migration. ECM components such as fibronectin may influence capillary morphogenesis by the generation of fragments that can modulate proliferation, migration, and protease activation. In the setting of diabetes, excess Fn is generated and is available for degradation. Thus, the production of Fn-f may be specifically relevant to the angiogenesis observed in proliferative diabetic retinopathy.     

A new class of tobacco chitinases homologous to bacterial exo-chitinases displays antifungal activity

A novel chitinase gene of tobacco was isolated and characterized by DNA sequence analysis of a genomic clone and a cDNA clone. Comparative sequence analysis of both clones showed an identity of 94%. The proteins encoded by these sequences do not correspond to any of the previously characterized plant chitinases of classes I-IV and are designated as class V chitinases. Comparison of the chitinase class V peptide sequence with sequences in the Swiss Protein databank revealed significant sequence similarity with bacterial exo-chitinases from Bacillus circulans, Serratia marcescens and Streptomyces plicatus. It was demonstrated that class V chitinase gene expression is induced after treatment of tobacco with different forms of stress, like TMV-infection, ethylene treatment, wounding or ultraviolet irradiation. Two related chitinase class V proteins of 41 and 43 kDa were purified from Samsun NN tobacco leaves inoculated with tobacco mosaic virus. The proteins were purified by Chelating Superose chromatography and gel filtration. In vitro assays demonstrated that class V chitinases have endo-chitinase activity and exhibit antifungal activity toward Trichoderma viride and Alternaria radicina. In addition, it was shown that class V chitinase acts synergistically with tobacco class I beta-1,3-glucanase against Fusarium solani germlings.     

Testicular lymphoma: a population-based study of incidence, clinicopathological correlations and prognosis. The Danish Lymphoma Study Group, LYFO

In a Danish population-based non-Hodgkin's lymphoma registry, 2687 newly diagnosed patients were registered from 1983 to 1992. 39 had testicular involvement (TL) (incidence 0.26/10(5)/year). Median age was 71 years. 24 cases had localised and 15 had disseminated disease. Histologically, all cases were diffuse (65% diffuse centroblastic type). Of the 27 tested, 11% were of T- and 89% of B-immunophenotype. In localised cases, where surgery was supplemented by combination chemotherapy (CCT), the relapse rate was 15.4%. The relapse rate for cases with localised disease treated with other regimens (orchiectomy and/or radiotherapy) was 63.6% (P < 0.05). Median relapse-free survival was 28 and 14 months, respectively. Overall 5-year survival for all cases was 17%. Adverse prognostic factors at the univariate level were stage IV, constitutional symptoms, serum lactic dehydrogenase elevation and performance score (WHO 3-4). It is suggested that the treatment of stage IE/IIE TL should include early CCT and CNS prophylaxis.     

Incorporating fuzzy membership functions into the perceptron algorithm

The perceptron algorithm, one of the class of gradient descent techniques, has been widely used in pattern recognition to determine linear decision boundaries. While this algorithm is guaranteed to converge to a separating hyperplane if the data are linearly separable, it exhibits erratic behavior if the data are not linearly separable. Fuzzy set theory is introduced into the perceptron algorithm to produce a ``fuzzy algorithm' which ameliorates the convergence problem in the nonseparable case. It is shown that the fuzzy perceptron, like its crisp counterpart, converges in the separable case. A method of generating membership functions is developed, and experimental results comparing the crisp to the fuzzy perceptron are presented.     

Characteristics of natural scenes related to the fractal dimension

Many objects in images of natural scenes are so complex and erratic, that describing them by the familiar models of classical geometry is inadequate. In this paper, we exploit the power of fractal geometry to generate global characteristics of natural scenes. In particular we are concerned with the following two questions: 1) Can we develop a measure which can distinguish between different global backgrounds (e.g., mountains and trees)? and 2) Can we develop a measure that is sensitive to change in distance (or scale)? We present a model based on fractional Brownian motion which will allow us to recover two characteristics related to the fractal dimension from silhouettes. The first characteristic is an estimate of the fractal dimension based on a least squares linear fit. We show that this feature is stable under a variety of real image conditions and use it to distinguish silhouettes of trees from silhouettes of mountains. Next we introduce a new theoretical concept called the average Holder constant and relate it mathematically to the fractal dimension. It is shown that this measurement is sensitive to scale in a predictable manner, and hence, provides the potential for use as a range indicator. Corroborating experimental results are presented.     

Energy Metabolites as Biomarkers in Ischemic and Dilated Cardiomyopathy

With more than 25 million people affected, heart failure (HF) is a global threat. As energy production pathways are known to play a pivotal role in HF, we sought here to identify key metabolic changes in ischemic- and non-ischemic HF by using a multi-OMICS approach. Serum metabolites and mRNAseq and epigenetic DNA methylation profiles were analyzed from blood and left ventricular heart biopsy specimens of the same individuals. In total we collected serum from n = 82 patients with Dilated Cardiomyopathy (DCM) and n = 51 controls in the screening stage. We identified several metabolites involved in glycolysis and citric acid cycle to be elevated up to 5.7-fold in DCM (p = 1.7 × 10⁻⁶). Interestingly, cardiac mRNA and epigenetic changes of genes encoding rate-limiting enzymes of these pathways could also be found and validated in our second stage of metabolite assessment in n = 52 DCM, n = 39 ischemic HF and n = 57 controls. In conclusion, we identified a new set of metabolomic biomarkers for HF. We were able to identify underlying biological cascades that potentially represent suitable intervention targets.     

Regional mass flux balancing for controlling gentle soil remediation operations

Extraction of heavy metals by accumulating plants is a method which is currently in development for the "gentle" remediation of contaminated agricultural soils (phytoremediation, see [2]). Areal contaminant mass flux balances are basic criteria for the design of such remediations and their control. A framework for the integration of contaminant balances relating the field scale of remediation with the regional scale of soil monitoring networks is provided by the recently developed method PROTERRA [3]. The objective of the study presented in this paper was to test the suitability of PROTERRA for planning and monitoring gentle soil remediations. For this purpose we applied the PROTERRA method to the contaminated agricultural land in and around Dornach, Switzerland, to assess copper flux balances.The calculations showed that atmospheric deposition and the application of pesticides and manure are important pathways for the inputs of copper. The copper export with a special maize cultivar accumulating heavy metals would be about three times higher than the average metal export with crops. A moderate increase of sewage sludge application would lead to a substantial increase of the copper input. Decisions to remediate the soil should take the uncertainty of mass flux balances both on field scale as well as on regional scale into account. Therefore, an important need of further development of the PROTERRA method is the integration of uncertainty analysis on both scales.